Expression of major histocompatibility antigens on pancreatic islet cells

Research output: Contribution to journalArticle

Abstract

Insulin-independent diabetes mellitus is often accompanied by manifestations of autoimmunity and is frequently associated with certain HLA haplotypes, predominantly DR3 and DR4. Because the major histocompatibility antigens are important determinants of the immune response in various tissues, we have investigated their expression on the pancreatic islet cells. Human, mouse, or rat islets of Langerhans, as well as lymphocytes or other differentiated cells, were biosynthetically labeled with radioactive amino acids, lysed in detergent, and immunoprecipitated with several antisera specific for major histocompatibility antigenic groups. The immunoprecipitates were analyzed by NaDodSo4/polyacrylamide gel electrophoresis under reducing conditions followed by autoradiography. The major histocompatibility antigens corresponding to the H-2K,D molecules in mice, the H1-A in rats, and the HLA-A, -B, and -C in humans were precipitated from both islet and lymphocyte lysates and were accompanied by β2-microglobulin. Binding of H-2 antibodies to islet cells was also confirmed by a radioligand assay using 125I-labeled protein A and by indirect immunofluorescence. Analyses in the fluorescence-activated cell sorter revealed that >95% of the cells in the beta-cell-rich fraction were fluorescent, providing further evidence that the pancreatic beta cells express the major histocompatibility antigens. Monoclonal antibodies or mouse alloantisera against HLA-DR or Ia antigens did not react with labeled pancreatic islet cell proteins.

Details

Authors
  • S. Baekkeskov
  • T. Kanatsuna
  • L. Klareskog
  • D. A. Nielsen
  • P. A. Peterson
  • A. H. Rubenstein
  • D. F. Steiner
  • A. Lernmark
External organisations
  • Hagedorn Research Institute
Original languageEnglish
Pages (from-to)6456-6460
JournalProceedings of the National Academy of Sciences of the United States of America
Volume78
Issue number10 I
Publication statusPublished - 1981 Jan 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes